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New research examines COVID-19 impact on aging brain

Thursday, September 24, 2020

Researchers at the University of Rochester Medical Center (URMC) and Duke University Medical Center will collaborate on a study that investigates why some older patients, who become severely ill from COVID-19, develop delirium that can lead to brain damage and a dementia diagnosis.

Nearly 30-percent of patients hospitalized with COVID-19 develop delirium – a state of confusion and impaired awareness. For severely ill patients the likelihood of delirium is closer to 70-percent. “The initial delirium, and then the cognitive, behavioral, and emotional problems – commonly known as dysexecutive syndrome – were arguably the most notable things in older people that had managed to survive COVID-19,” said Harris Gelbard, M.D., Ph.D. Professor and Director, Center for Neurotherapeutics Discovery, who is also the principal investigator at URMC on this study which is being funded by the National Institute of Aging. “Nobody knows whether that's permanent or not because of the advanced age of the people this is impacting.”

Using a model for inhaled lipopolysaccharide-based acute lung injury in mice to mimic what happens in the lungs of a severally ill COVID-19 patient, Gelbard and his colleague Niccolo Terrando, Ph.D. at Duke University Medical Center will look for specific events in the neurovascular unit —brain endothelial cells and their blood-brain barrier (BBB) forming tight junctions that support the central nervous system – that can be traced back to cognitive impairment. Part of the hypothesis Gelbard is investigating is that scarring in the lung may cause platelets and inflammatory white cells to migrate to blood vessels in the central nervous system with the white cells traversing the BBB to cause neurologic disease. “The goal is to establish what the prerequisites are for lung injury that will lead to brain injury. And at that point, then we can start asking more complicated questions.”

The researchers will also investigate how the body responds to URMC-099, an anti-inflammatory and neuroprotective agent developed by Gelbard, to prevent these sequelae. The use of behavior analysis at Duke and in vivo brain imaging at URMC will determine delirium-like changes in the mice.

Gelbard and Terrando are confident that this study will lead to a larger and longer study of the impact COVID-19 has on the brain of an older population. “If you could do something to prevent that in the first place, chances are you are going to do better, down the road.”

Read More: New research examines COVID-19 impact on aging brain

Program to Create National Model of Support for Parkinson’s Patients

Tuesday, September 22, 2020

The University of Rochester Medical Center (URMC) in collaboration with the Parkinson’s Foundation is developing a palliative care program that will be become the standard of care in the organization’s 33 Centers of Excellence clinics across the U.S. 

The initiative – which is being funding with $1.6 million in support from the federal Patient-Centered Outcomes Research Institute (PCORI) – is led by URMC neurologist Benzi Kluger, M.D., a professor of Neurology and Medicine and director of URMC’s new Palliative Care Research Center.

Kluger and his current and former colleagues in Rochester and the University of Colorado have developed an innovative model of palliative care delivery consisting of interdisciplinary teams of providers that address the needs of Parkinson’s patients and their families as they grapple with the physical, emotional, social, and spiritual symptoms of their disease.  In a previous PCORI-funded study published earlier this year in JAMA Neurology, Kluger and his team demonstrated that outpatient palliative care improves quality of life and other outcomes, including reductions in caregiver burden and improvement in motor symptoms. 

The Parkinson’s Foundation Centers of Excellence program recognizes medical centers that have brought together teams of neurologists, movement disorder specialists, physical and occupational therapists, and mental health professionals, and provide high levels of support and care for Parkinson’s patients.

Kluger and his team are developing virtual training programs tailored to the unique needs and circumstances of each clinic.   The program will provide caregivers with the tools, resources, and skills to deliver a patient-centered model of care that effectively addresses psychosocial issues patients are experiencing, provides support to families and care partners, screens for non-motor symptoms like pain and depression, and encourages the development of advanced care roadmaps for individual patients.

Nedergaard Honored for Alzheimer’s Research

Tuesday, September 15, 2020

Maiken Nedergaard, M.D., D.M.Sc. has been awarded the International Prize for Translational Neuroscience of the Gertrud Reemtsma Foundation for her research in the glymphatic system, the brain’s unique waste removal process. 

Nedergaard’s research was recognized by the Foundation for findings that “offer new approaches for treatments and preventive measures for Alzheimer’s and other neurodegenerative diseases.”

First discovered by researchers in the URMC Center for Translational Neuromedicine in 2012, the glymphatic system piggybacks on blood vessels and pumps cerebrospinal fluid, washing waste from the brain.  The accumulation of toxic proteins like beta amyloid are linked neurological disorders, including Alzheimer’s disease.  Nedergaard’s lab has since gone on to show how sleep disruption, age, and injury can impair the brain’s ability to effectively remove waste.

Nedergaard was presented the award at a ceremony at the Max Plank Society in Cologne, Germany on September 10. 

URMC Tapped to Advance Research in Intellectual and Developmental Disabilities

Wednesday, July 8, 2020

 The University of Rochester has been designated an Intellectual and Developmental Disabilities Research Center (IDDRC) by the National Institute of Child Health and Human Development (NICHD). The award recognizes the Medical Center’s national leadership in research for conditions such Autism, Batten disease, and Rett syndrome, will translate scientific insights into new ways to diagnose and treat these conditions, and provide patients and families access to cutting edge care.

The IDDRC at the University of Rochester will be led by John Foxe, Ph.D., director of the Del Monte Institute for Neuroscience, and Jonathan Mink, M.D., Ph.D., chief of Child Neurology at Golisano Children’s Hospital. The designation is accompanied with more than $6 million in funding from NICHD.

Read More: URMC Tapped to Advance Research in Intellectual and Developmental Disabilities

New Therapy Reduces Chronic Low Back Pain in Large International Study

Friday, June 19, 2020

A new study hasfound that tanezumab, a monoclonal antibody that inhibits nerve activity, provides relief in patients with chronic low back pain, one of the leading reasons why people seek medical care and the number one cause of disability worldwide.

“This demonstration of efficacy is a major breakthrough in the global search to develop non-opioid treatments for chronic pain,” said John Markman, M.D., director of the Translational Pain Research Program in the University of Rochester Medical Center (URMC) Department of Neurosurgery and lead author of the study which appears in the journal Pain. “There were also improvements in function linked to the reduction in pain severity.”  

This is the first study that shows long-term relief for chronic low back pain with a single dose of tanezumab delivered under the skin once every two months. The study was conducted in 191 sites across eight countries in North America, Europe, and Asia.

Researchers are increasingly finding that certain proteins circulating in the bloodstream heighten the sensitivity of cells in the nervous system to pain. One of these proteins, called nerve growth factor (NGF), may explain why some individuals experience more intense and chronic back pain.  Tanezumab is an NGF inhibitor.

The patients with chronic low back pain enrolled in this study did not previously have relief with at least three different types of pain medication, including opioids, and were considered “difficult-to-treat.” Patients with symptoms, signs, and x-ray evidence of moderate-to-severe osteoarthritis, a disorder commonly found in older patients with chronic low back pain, were excluded from the study.

Read More: New Therapy Reduces Chronic Low Back Pain in Large International Study

Animal Study Shows Human Brain Cells Repair Damage in Multiple Sclerosis

Tuesday, May 19, 2020

A new study shows that when specific human brain cells are transplanted into animal models of multiple sclerosis and other white matter diseases, the cells repair damage and restore function.  The study provides one of the final pieces of scientific evidence necessary to advance this treatment strategy to clinical trials.

“These findings demonstrate that through the transplantation of human glial cells, we can effectively achieve remyelination in the adult brain, ” Steve Goldman, M.D., Ph.D., professor of Neurology and Neuroscience at the University of Rochester Medical Center (URMC), co-director of the Center for Translational Neuromedicine, and lead author of the study.  “These findings have significant therapeutics implications and represent a proof-of-concept for future clinical trials for multiple sclerosis and potential other neurodegenerative diseases.”

The findings, which appear in the journal Cell Reports, are the culmination of more than 15 years of research at URMC understanding support cells found in the brain called glia, how the cells develop and function, and their role in neurological disorders. 

Goldman’s lab has developed techniques to manipulate the chemical signaling of embryonic and induced pluripotent stem cells to create glia.  A subtype of these, called glial progenitor cells, gives rise to the brain’s main support cells, astrocytes and oligodendrocytes, which play important roles in the health and signaling function of nerve cells. 

Read More: Animal Study Shows Human Brain Cells Repair Damage in Multiple Sclerosis

Study by John Markman Points to New Way of Assessing Patient Pain

Monday, April 20, 2020

The professor of Neurosurgery and Neurology found that asking, "Is your pain tolerable" in conjunction with the traditional 0-10 scale can help doctors better understand whether treatment — including opioids — is necessary.

Read More: Study by John Markman Points to New Way of Assessing Patient Pain

New COVID-19 Neurology Link

Wednesday, March 25, 2020

We have added a new link to the Neurology Intranet Page under the General Links to the left. Clicking on the COVID-19 Neurology link will take you to a BOX folder with access to files containing current COVID-19 information related to Neurology. If you are not logged into BOX, you will be prompted to log in. If you do not have a BOX account, please contact NeurologyIT at 5-0431 and they will create an account for you.

New Book Details Roadmap to Prevent and Treat Parkinson’s

Wednesday, March 11, 2020

A new book titled “Ending Parkinson’s Disease: A Prescription for Action” and authored by University of Rochester Medical Center neurologist Ray Dorsey, M.D. and his colleagues, lays out a new vision to prevent, advocate for, care for, and treat this major and growing global health threat. 

“Parkinson’s disease is a looming pandemic and we are woefully unprepared to meet this challenge – many people remain undiagnosed and untreated, research funding for the disease has stagnated, and the most effective treatment is now a half century old,” said Dorsey, the David M. Levy Professor of Neurology and director of the Center for Health + Technology (CHeT). “At least some cases of Parkinson’s are man-made and, therefore, preventable.”

Parkinson's disease is the fastest growing neurological disorder in the world, outpacing Alzheimer’s.Over the past 25 years, the number of people with the condition has jumped from three million to more than six million, and by 2040, it is projected to double again.

First described in early 18th century London at the height of the Industrial Revolution, Parkinson’s and its rise have been fueled by environmental exposures to harmful chemicals. The two biggest culprits currently still in use are paraquat, a herbicide widely used in the U.S. despite being banned in 32 countries, and trichloroethylene (TCE), a solvent used in a wide range of industrial and consumer products. Not only are agricultural and industrial workers at risk of exposure, but these chemicals also enter the food chain, water supply, reside in the soil in brownfield sites, and impact indoor air quality. 

The authors also advocate removing barriers to care. For example, over 40 percent of individuals with the disease do not see a neurologist soon after diagnosis, primarily because of where they live. Technologies like telemedicine have been shown to deliver effective specialized care to patients and improves their lives. However, Medicare policies often do not pay for these services. 

Confronting the Parkinson’s pandemic will require marshalling the same focus and resources employed with success to address other public health challenges, such as polio, HIV, and breast cancer. The authors label their course of action PACT: prevent the disease, advocate for policies and resources, care for all affected, and treat the condition with new and more effective therapies.

URMC has a long been a leader in the field of Parkinson’s research and care. Medical Center researchers were instrumental in conducting pivotal clinical trials that led to at least four FDA-approved drugs currently treat the disease. CHeT is a leading center for the application of new technologies to study and assess Parkinson’s. The themes detailed in the book will form the basis of a new initiative launched by URMC in the coming months that will focus on the research, grassroots advocacy, and public policy steps necessary to prevent the disease and expand access to care.

Additional co-authors of the book include Todd Sherer, Ph.D., CEO of the Michael J. Fox Foundation, Mike Okun, M.D., with the University of Florida, and Bastiaan R. Bloem, M.D., Ph.D., with Radboud University in the Netherlands. Proceeds from sales of the book will support Parkinson’s research at URMC and other institutions.

Read More: New Book Details Roadmap to Prevent and Treat Parkinson’s

Kluger to Lead New Palliative Care Research Initiative

Wednesday, March 4, 2020

Benzi Kluger, M.D., has been tapped to lead palliative care research across URMC. Kluger comes to URMC from the University of Colorado School of Medicine and started at the Medical Center on January 1. 

Kluger, who has been appointed a professor of Neurology and Medicine, is the director of URMC’s new Palliative Care Research Center within the Department of Medicine. In this role, he will develop resources and core infrastructure to enable researchers and clinicians from across the University to undertake palliative care research projects.

“Dr. Kluger has established himself as a leading researcher and scholar in both neurological disorders and palliative care,” said Bob Holloway, M.D., M.P.H., chair of the Department of Neurology. “We are fortunate to have recruited him to Rochester and look forward to helping him have a major impact on the field of palliative care.” 

“In his young and blossoming career Benzi has already gained international recognition as a productive, creative scholar in the realm of innovative palliative care delivery models,” said Robert Horowitz, MD, chief of the Palliative Care Division at URMC. “He is an ambitious, generative, and prolific scholar, clinician, teacher and human being, with an explicit commitment to building ties across UR schools, departments, and divisions.”

Kluger’s specific interest is in innovative models of palliative care delivery, in which an interdisciplinary team addresses the many needs of seriously ill patients and their families, as they grapple with the physical, emotional, social, and spiritual symptoms of their disease. Kluger is working with faculty in the Wilmot Cancer Center, Divisions of Palliative Care and Nephrology, the School of Nursing, and other Medical Center departments and divisions to develop and evaluate integrated models of outpatient palliative care.  Kluger will also oversee the creation of a new Neuropalliative Care Division within the Department of Neurology.  

With support from a PCORI grant, Kluger led a multisite randomized controlled trial in Colorado that compared the effectiveness of multidisciplinary outpatient palliative care integrated with standard care versus standard care alone for Parkinson’s patients.  The results of the study, which were published earlier this month in JAMA Neurology, showed that outpatient palliative care improves quality of life and other outcomes, including reductions in caregiver burden and improvement in motor symptoms. 

"Palliative care provides a framework to address the multiple needs of patient populations from the time of diagnosis and is particularly beneficial when people reach more into more advanced stages of illness where our traditional care models have less to offer," said Kluger.  “This effort is part of a wider movement to make palliative care a standard and expected part of care for persons living with serious diseases.”

Kluger conducted his Medical and Neurology Residency training at the University of Colorado. He completed fellowship training in Behavioral Neurology and Movement Disorders at the University of Florida.  He recently established the International Society of Neuropalliative Care (ISPN), which has members from US, Canada, Europe, Asia and Australia, and will be the organization’s first president. Kluger and Holloway are co-editors of the book “Neuropalliative Care: A Guide to Improving the Lives of Patients and Families Affected by Neurological Disease.”

The ANA Q&A: Neurology Research in Sub-Saharan Africa

Tuesday, March 3, 2020

"One hears a lot about malaria deaths, but the sad reality is that a third of survivors sustain a brain injury with associated neurological sequelae. More than 200,000 African children each year end up with neurodisabilities from malaria. This is low-hanging fruit for decreasing the global burden of neurological disease and increasing the human capacity in this region of the world."

~Gretchen Birbeck, M.D., M.P.H., Professor of Neurology, ANA International Outreach Committee Chair 

To celebrate International Women’s Day (March 8), we’re highlighting ANA members who are doing impressive work both domestically and abroad. Keep reading for our interview with Gretchen Birbeck, M.D., M.P.H. Dr. Birbeck is a neurologist who divides her time between the U.S. and Africa. Her U.S. academic home is the University of Rochester, where she is the Rykenboer Professor of Neurology. She also serves as chair of the ANA’s International Outreach Committee.

We spoke with her to learn more about her research, her work with the International Outreach Committee, and what the theme of this year’s International Women’s Day, “Each for Equal,” means to her.

Can you give an overview of the initiatives you've been working on in Zambia?

My work in Zambia really mirrors what an academic neurologist does anywhere—I teach, provide clinical care and conduct research.  And for me the split is about 70/30 with the largest proportion of my time being spent on research activities.

On the research front, I am the Principal Investigator for three NIH-funded R01s. The ChASE study is a Cohort Study of HIV-Associated Seizures and Epilepsy. One of the clinical challenges in providing neurological care in sub-Saharan Africa is knowing what to do for someone who is HIV infected presenting with new onset seizure. Epidemiological data that otherwise informs if and when to start a chronic antiseizure medication may not apply to persons with HIV especially if an HIV-associated drug reaction or opportunistic infection has precipitated the seizure. And unfortunately, the choice of seizure medications may be limited to enzyme-inducing agents that interact with antiretroviral medications. ChASE is providing some insights on what causes seizures in this population, who is at risk of long-term seizure disorders and what happens when the seizure medications available in HIV endemic regions are combined with the HIV medications used locally. This is an especially dynamic study as it involves adults and children in rural and urban populations. I spent the first two decades of my time in Zambia based in a rural area and I still have excellent research teams and colleagues there so it is wonderful to remain working and engaged with them even though I am now based primarily in Lusaka.

I am also working on the Malaria Fever study which is a randomized controlled trial (RCT) of aggressive antipyretic therapy using maximal dose ibuprofen and acetaminophen for fever control in pediatric malaria. My K23 project was a prospective cohort study of neurological outcomes in pediatric cerebral malaria survivors. Since completing my K23, I’ve been working down the list of potentially modifiable risk factors for brain injury in this population hoping to eventually conduct a multi-country RCT of a neuroprotective “package” of care to improve outcomes in child survivors of cerebral malaria. One hears a lot about malaria deaths, but the sad reality is that a third of survivors sustain a brain injury with associated neurological sequelae. More than 200,000 African children each year end up with neurodisabilities from malaria. This is low-hanging fruit for decreasing the global burden of neurological disease and increasing the human capacity in this region of the world. I also think what we learn about epileptogenesis from the cerebral malaria model may help us understand the process in general and this has implications for advances in neurological care everywhere.

Finally, the MRI Ancillary Grant is an imaging study of children enrolled in the Malaria Fever study. This is evaluating structural evidence of brain injury to potentially identify neuroprotective effects and/or side effects from the antipyretics that won’t necessarily be mediated by fever control. This is really an important additional outcome for the RCT since it is quite possible that the anti-inflammatory benefits of the antipyretics might be neuroprotective yet not significantly reduce fever. But the addition of imaging may also help us better identify adverse effects from the antipyretics. One of the neurological phenomena that occurs in pediatric cerebral malaria is the development of brain microhemorrhages. These feature prominently among autopsy findings and, more recently, our research team identified microhemorrhages in children who survived cerebral malaria. So, one major concern is that children who receive ibuprofen (which is not standard of care for malaria fevers) may have an increased risk of microhemorrhages or frank bleeding. The MRI Ancillary Grant will allow us to see if this is occurring.

Clinically, I have an epilepsy clinic in rural Zambia that I staff weekly, I pinch hit for attending on child neurology consults when needed on the inpatient service and I read EEGs Zambia at the University Teaching Hospitals (UTH) Children’s Hospital and Malawi for Queen Elizabeth Central Hospital’s Pediatric service.

On the teaching front, there is a new postgraduate training program in neurology now at UTH and it is doing an amazing job of transforming care and education here. I can’t take any credit for the program, which is led by Dr. Deanna Saylor (Johns Hopkins) and was co-founded by Dr. Omar Siddiqi (Beth Israel at Harvard), but I will proclaim myself to be the program’s biggest cheerleader. And in this vibrant environment, I’m able to spend my medical education endeavors primarily as a mentor for young researchers, both American and African. My mentees study stigma, nutritional neuropathies, cognition in adolescents with HIV, TB meningitis, the impact of health system structure on neurological care delivery, CNS IRIS, and comorbid HIV and NCDs.

So, things are busy and chaotic, but never boring!

Read More: The ANA Q&A: Neurology Research in Sub-Saharan Africa

Parkinson's Foundation Charity Hockey Game

Friday, January 17, 2020

Hockey Benefit

The Parkinson’s foundation is putting on a charity hockey game Saturday February 8th from 4-6pm. I will be participating in the event showing washed up NHL players how it’s done along with raising money by selling tickets for a good foundation and cause so anyone that can make the game and support it would be amazing! They are asking players to sell tickets (in the “purchasing from a player” box (Here's the link)) and I thought who better to ask than the people that work hands on with Parkinson’s disease. Thanks, everyone!

Justin Alves,
Human Subject Research Coordinator

Read More: Parkinson's Foundation Charity Hockey Game

Welcome Resident Applicants

Tuesday, January 7, 2020

photo of a wedge of cheddar cheese and a glass of red wine

The Department of Neurology would like to welcome residency applicants, interviewing on Monday, January 13th. A wine and cheese reception for the applicants will be held from 4:00 - 4:30 PM in the Garvey Room. All Faculty & Residents are invited to attend.

Adult Neurology Applicants

Blake Beehler – Rush Medical College
Christopher Brewer – University of Tennessee Health Science Center
Kim Griffin – Medical College of Wisconsin
Lauren Herrera – University of Cincinnati
Zachary Roesch – Creighton University
Deborah Rose – Loyola University
Carlos Sollero – University of Rio de Janeiro, Brazil